Engineered yeast: a breakthrough in targeted cancer therapies

Interviewer: Today, we're joined by Prof. Gautam Dantas from the Washington University School of Medicine to discuss his recent work developing a novel yeast-based system for delivering immune checkpoint inhibitors directed to gastrointestinal tumors using engineered probiotics. Prof. Dantas, thank you very much for joining us today. Prof. Dantas: My pleasure. Thank you for having me. Interviewer: To start, can you explain the rationale behind using yeast rather than bacteria as a vehicle for delivering immune checkpoint inhibitors or ICIs? Prof. Dantas: Yes. Happy to do so. So, as you're alluding to, there are multiple different microorganisms that are candidate chassis for delivering therapeutics in the human body. There's been a lot of exciting work done on engineering bacteria to produce molecules like immune checkpoint inhibitors, and they certainly have lots of benefits because a lot of work has been done in engineering bacteria. But we have a couple of potential limitations. One, there are a lot of other bacteria in the gut, as an example, and one of the things that bacteria can do that you and I can't very well, is horizontal gene transfer. That is this incredible ability that they have to rapidly move fragments of DNA between pretty unrelated organisms, and in doing so, exchange genotypes and phenotypes. One of the big concerns there is that microorganisms that are brought into a body habitat may either donate their genes over to the commensal microbiota, or they might pick up genes from the commensal microbiota. This is a hallmark problem with pathogens, as they course through the body. That's one of the singular concerns with using bacterial probiotics is that,